Effect of Predeparture Testing on Postarrival SARS-CoV-2–Positive Test Results Among International Travelers — CDC Traveler-Based Genomic Surveillance Program, Four U.S. Airports, March–September 2022

Beginning December 6, 2021, all international air passengers boarding flights to the United States were required to show either a negative result from a SARS-CoV-2 viral test taken ≤1 day before departure or proof of recovery from COVID-19 within the preceding 90 days (1). As of June 12, 2022, predeparture testing was no longer mandatory but remained recommended by CDC (2,3). Various modeling studies have estimated that predeparture testing the day before or the day of air travel reduces transmission or importation of SARS-CoV-2 by 31%-76% (4-7). Postarrival SARS-CoV-2 pooled testing data from CDC's Traveler-based Genomic Surveillance program were used to compare SARS-CoV-2 test results among volunteer travelers arriving at four U.S. airports during two 12-week periods: March 20-June 11, 2022, when predeparture testing was required, and June 12-September 3, 2022, when predeparture testing was not required. In a multivariable logistic regression model, pooled nasal swab specimens collected during March 20-June 11 were 52% less likely to be positive for SARS-CoV-2 than were those collected during June 12-September 3, after adjusting for COVID-19 incidence in the flight's country of origin, sample pool size, and collection airport (adjusted odds ratio [aOR] = 0.48, 95% CI = 0.39-0.58) (p<0.001). These findings support predeparture testing as a tool for reducing travel-associated SARS-CoV-2 transmission and provide important real-world evidence that can guide decisions for future outbreaks and pandemics.

the airport, dry nasal swab samples were pooled (5-25 samples per pool) by the flight country of origin. Pooled samples were sent to a laboratory in the Ginkgo Bioworks laboratory network for SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing (8).
Postarrival RT-PCR testing results during March 20-June 11, when the predeparture test requirement was in effect, were compared with those during June 12-September 3, when predeparture testing was voluntary. To account for worldwide differences in COVID-19 incidence, pooled test results were matched with daily 7-day average country-level COVID-19 incidence (cases per 100,000 population) from the World Health Organization* based on pool collection date and the flight country of origin. To account for reporting differences by country, normalized incidence was estimated by dividing the 7-day average COVID-19 incidence on the date of pool collection for the flight country of origin by the maximum 7-day average daily incidence for that country during March 20-September 3, then multiplying by 100.
To identify factors associated with positive postarrival SARS-CoV-2 pooled test results, bivariate comparisons and univariable logistic regression were performed. Factors with significant univariable associations (p<0.05) were incorporated into a multivariable mixed effects logistic regression model that included collection airport as a random effect. Alternative periods (during the 4-8 weeks preceding June 12 and those on or after that date) were considered in sensitivity analyses. Analyses were conducted in R (version 4.0.2; R Foundation). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. † During March 20-September 3, 2022, a total of 28,056 arriving travelers from 24 countries received testing for SARS-CoV-2, yielding 3,049 pooled samples with a median of eight participant samples per pool (range = 5-25). During March 20-June 11, among 16,668 Traveler-based Genomic Surveillance participants, 13,190 (79.1%) reported having had a predeparture test; during June 12-September 3, this percentage declined by 80% to 1,786 of 11,123 (16.1%) participants reporting having had a predeparture test (Figure 1). Among  Table 1, https://stacks.cdc.gov/view/cdc/124584). The increase in the percentage of positive postarrival test results between March 20-June 11 and June 12-September 3 occurred across countries, collection airports, incidences, and pool sizes and was apparent in both bivariate analyses and univariable logistic regression. Participants during each period were similar in age and gender; however, during the period beginning June 12, fewer participants reported U.S. residency (Supplementary Table 2, https://stacks.cdc.gov/view/cdc/124585).
Multivariable model results showed that pools of samples collected during March 20-June 11 (when predeparture testing was mandatory) were 52% less likely to be positive than were those when predeparture testing was voluntary (aOR = 0.48, 95% CI = 0.39-0.58) (p<0.001), after adjusting for COVID-19 incidence in the flight's country of origin, pool size, and collection airport (Table). COVID-19 incidence in the flight's country of origin and pool size also remained significant predictors of positive pooled test results in the multivariable model.  Table 3, https://stacks.cdc.gov/ view/cdc/124586).

Discussion
Postarrival SARS-CoV-2 test results were 52% less likely to be positive when the predeparture COVID-19 testing requirement was in effect than during the 12-week period after it was discontinued; this finding was true even when controlling for other factors such as incidence in the flight's country of origin and pool size. These findings, based on observed, real-world traveler data, support the value of predeparture testing as a tool for reducing SARS-CoV-2 transmission associated with travel and were consistent with estimates from previous modeling studies (4-7).
Sensitivity analyses using shorter time frames around removal of the predeparture testing requirement produced similar findings. Although still statistically significant, the magnitude of this effect decreased when 4-week windows were considered, possibly because of smaller sample sizes during the shorter time frame or higher rates of voluntary predeparture testing during the 4 weeks after the removal of the predeparture test requirement on June 12.
The findings in this report are subject to at least five limitations. First, because participation in the Traveler-based Genomic Surveillance Program is voluntary, results might not be representative of all international travelers; however, any participation bias was likely consistent across both periods. Second, because of the pooled sampling and testing strategy employed, trends among individual participants could not be assessed. Third, incidence data were matched with pooled test results based on a flight's country of origin, and it is possible that participants began their itinerary in a different country and later connected to the U.S.-bound flight. Fourth, as testing rates decline globally, reported incidence data might not fully reflect actual COVID-19 risk in a given country (9). Finally,  Reducing the number of persons traveling while infected with SARS-CoV-2 through predeparture testing could reduce air travel-associated transmission in airports, aircraft, and destination communities. CDC continues to recommend testing before and after international travel (3). Along with other strategies, including isolation of persons with confirmed or suspected COVID-19 and masking, testing before international travel is an important element of a multipronged COVID-19 prevention strategy. In December 2022, results from this analysis were used alongside other evidence to support a predeparture test requirement for travelers boarding flights to the United States from China to slow importation of SARS-CoV-2 during a surge in COVID-19 cases there (10). These findings provide important real-world evidence supporting the effectiveness of predeparture testing that can guide decisions for future outbreaks and pandemics.

Summary
What is already known about this topic?
During December 6, 2021-June 11, 2022, SARS-CoV-2 testing ≤1 day before departure or proof of recent COVID-19 recovery were required for passengers boarding U.S.-bound flights. Mathematical models have estimated predeparture testing effectiveness in preventing travel-associated transmission.
What is added by this report?
What are the implications for public health practice?
Predeparture testing can reduce SARS-CoV-2 transmission risk during or after travel by reducing the number of infectious travelers. These results can help guide decisions for future outbreaks.